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Pharm Exam 4 > Anti-Metabolites > Flashcards

Anti-Metabolites Flashcards

1
Q

What are the anti-metabolites ?

A

Folate Antagonists

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2
Q

What is Tetrahydrofolic acid?

A

Acid required for DNA/RNA synthesis (purine and pyrimidine synthesis)

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3
Q

What happens to the folic acid that humans receive from their diet?

A

It get converted to DHF

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4
Q

How do bacteria synthesize Folic acid?

A

They use paraminobenzoic acid (PABA) to synthesize DHF then DHF converts it to THF

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5
Q

Name the 6 PABA analogs inhibitors.

A
  1. Sulfamethazole–newer
  2. Sulfasalazine–GI
  3. Silver Sulfadiazine-topical
  4. Sulfisoxazole-ophthalmic
  5. Dapsone-leprosy
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6
Q

Name the 3 DHF reductase inhibitors.

A
  1. Trimethoprim
  2. Pyrimethamine
  3. Proguanil (Also Methotrexate)
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7
Q

Name the 2 combinations.

A
  1. Cotrimoxazole

2. Fansidar

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8
Q

What is Cotrimoxazole (Bactrim/Septra) a combination of?

A

Trimethoprim + Sulfamethoxazole

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9
Q

What is Fansidar a combination of?

A

Sulfadoxine + Pyrimethamine

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10
Q

Are the Sulfa PABA Analogs STATIC or CIDAL?

A

STATIC

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11
Q

What are the Sulfa PABA Analogs active against?

A

Gram (+) and gram (-)

  1. Selected enterobacteria (UTI)
  2. Chlamydia
  3. Pneumocystis
  4. Nocardia
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12
Q

If given topically, what are the Sulfa PABA drugs are used for?

A

prevent infections of burns

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13
Q

What can you treat newborns with prophylactically if there is a Trachoma (Chlamydial) inf?

A

Erythromycin ointment or silver nitrate solution

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14
Q

What is the most common cause of preventable blindness?

A

Chlamydia

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15
Q

How are Sulfa-PABA drugs absorbed?

A 
very well orally 
EXCEPT: 
Sulfasalazine (chronic bowel disease) 
and 
Succinylsulfathiazole (salmonella and shigella carriers)
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16
Q

Which Sulfa-PABA drug is given topically to decrease burn sepsis but has a superinfection risk with fungi?

A
  1. Silver sulfadiazine

2. Mafenide (sulfamylon) but this is painful

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17
Q

Do the Sulfa-PABA analog drugs penetrate the CSF?

A

yes; even without inflammation

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18
Q

Do the Sulfa-PABA analog drugs penetrate the placental barrier?

A

Yes

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19
Q

There are 2 other important places the Sulfa PABA analog drugs go into besides the CSF and placenta–what are they?

A
  1. Breast milk

2. Bound to serum albumin

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20
Q

Why should we be worried that the Sulfa-PABA analog drugs get bound to the serum albumin?

A

In a newborn, it can cause kernicterus by displacing the bilirubin

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21
Q

What 2 drugs do the Sulfa-PABA drugs interact with?

A
  1. Increase Warfarin

2. Methotrexate

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22
Q

Which drug can cause crystalluria? And how does this happen?

A

Sulfa PABA analog drugs

they can precipitate at neutral or acidic pH then that causes the cystalluria

23
Q

Since crystalluria is nephrotoxicity, what can you instruct the patient to do to prevent this?

A
  1. Adequate hydration

2. Alkalization of urine –> drug ionization

24
Q

Which Sulfa PABA analog drugs are more soluble at urinary pH and thus, have less chance of crystalluria?

A
  1. Sulfisoxazole

2. Sulfamethoxazole

25
Q

What are some hypersensitivity reactions of the Sulfa PABA analog drugs?

A
  1. Rashes
  2. Photosensitivity
  3. Angioedema
    (Urticaria and edematous areas)
26
Q

What adverse effect will you expect from a longer acting Sulfa PABA drug?

A

Stevens-Johnson Syndrome

27
Q

Which diuretics do the Sulfa PABA drugs have cross reactivity?

A
  1. Acetazolamide
  2. Thiazides
  3. Furosemide
    Bumetanide
28
Q

Which antihypertensive drugs have cross reactivity with the Sulfa PABA drugs?

A

Diazoxide

29
Q

Which hypoglycemic agents have cross reactivity with Sulfa PABA drugs?

A

The Sulfonylureas:

  1. Tolbutamide
  2. Glyburide
  3. Glipizide
30
Q

Which classes of drugs have cross reactivity with the Sulfa PABA drugs?

A
  1. Diuretics
  2. Antihypertensive drugs
  3. Sulfonylurea hypoglycemic drugs
31
Q

What hemopoietic disturbances do the Sulfa PABA analog drugs have?

A
  1. Hemolytic anemia G 6 PD deficiency
  2. Granulocytopenia
  3. Thrombocytopenia
32
Q

What kind of drug potentiation do the Sulfa PABA analog drugs have on:

  1. Tolbutamide: ?
  2. ?: increases anticoagulation
  3. ?: increases toxicity
  4. Increased free bilirubin
A
  1. increases hypoglycemic effect
  2. Warfarin
  3. Methotrexate
  4. Kernicterus
33
Q

What contraindications do the Sulfa PABA analog drugs have?

A
  1. Pregnant and lactating women
  2. Avoid Sulfa-PABA drugs in newborns
  3. Pts taking Methamine
34
Q

Why should Sulfa PABA analogs be avoided in newborns?

A

Because the bilirubin will get displaced by the drug, causing the bilirubin to enter the CNS causing mental dysfunction

35
Q

Why would you not give a patient taking methamine a Sulfa PABA drug?

A

Because the Sulfonamides condense with formaldehyde

36
Q

A mutated bacterial dihydropteroate synthetase is a resistance mechanism to which drug?

A

Sulfa PABA drugs

37
Q

What is Trimethoprim?

A

Potent inhibitor of bacterial dihydrofolate reductase (DHFR)

decreases folate coenzymes for dna/rna synthesis

38
Q

T or F: Trimethoprim has an antibacterial spectrum similar to the sulfonamides but 2x as stronger

A

False: they are 20-50x stronger

39
Q

What is the MOA of Trimethoprim?

A

Bacterial reductase

40
Q

What is nice about Trimethoprim?

A

It has good selective toxicity

41
Q

Which drug is Trimethoprim most often compounded with?

A

Sulfamethoxazole

42
Q

An altered dihydrofolate reductase with decreased affinity for the drug is a resistance mechanism for which drug?

A

Trimethoprim

43
Q

Which drug has increased concentrations in prostatic and vaginal fluid along with a folate deficiency?

A

Trimethoprim

44
Q

What is an effect of the folate deficiency using the treatment of Trimethoprim?

A

Megaloblastic anemia

45
Q

How do you treat the megaloblastic anemia caused by Trimethoprim?

A

reverse with concurrent folinic acid (leucovorin)

46
Q

What is the benefit of treating a pt with Co-trimoxazole?

A

Synergism: inhibition of 2 sequential steps–

  1. competitive inhibition of folic acid synthesis (PABA analog)
  2. Selective inhibition of bacterial dihydrofolic acid reductase
47
Q

What combination is Fansidar?

A

Pyrimethamine + Sulfaxodine

48
Q

Why would you need to use Fansidar?

A

Chloroquinine-resistant malaria

49
Q

What is the benefit of Fansidar?

A

Synergism: inhibition of 2 sequential steps–

  1. competitive inhibition of folic acid synthesis (PABA analog)
  2. Selective inhibition of bacterial dihydrofolic acid reductase
50
Q

What are some adverse reactions to Fansidar?

A
  1. Rash
  2. N/V; glossitis, stomatitis
  3. Megaloblastic anemia
  4. G6PD-deficiency = hemolytic anemia
  5. HIV + pneumocystitis + Bactrim = drug fever, rashes, diarrhea, maybe pancytopenia
51
Q

What 3 drugs should you have caution with when prescribing Fansidar?

A
  1. Warfarin
  2. Phenytoin
  3. Methotrexate

ALL increase

52
Q

What are some common therapeutic uses for Fansidar?

A
  1. UTI
  2. Bacterial Respiratory Tract inf
  3. Pneumocystis carinii pneumonia (PCP)
  4. GI inf
  5. Mild burns, topically
53
Q

If you are treating mild burns with Fansidar, HOW should it be administered?

A

Topically

Pharm Exam 4 (10 decks)

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